Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L
Exercise-induced enhancement of synaptic function triggered by the inverse BAR protein, Mtss1L
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DOI：
10.7554/elife.45920
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发表时间：
2019-06-24
期刊：
影响因子：
7.7
通讯作者：
Westbrook, Gary L.
中科院分区：
文献类型：
--
作者：
Chatzi, Christina;Zhang, Yingyu;Westbrook, Gary L.
运动是学习和记忆的有效增强剂，但我们对可能包括海马体突触功效改变在内的潜在机制知之甚少。为了解决这个问题，我们将小鼠暴露于单次自愿运动，并使用条件性Fos-TRAP小鼠永久标记激活的成熟海马齿状颗粒细胞。运动激活的神经元（Fos-TRAPed）在运动后3天表现出树突棘和兴奋性突触后电流的输入选择性增加，表明运动诱导的结构可塑性。激活神经元的激光捕获显微切割和RNASeq显示，最高度诱导的转录本是Mts 1 L，这是一种很少研究的含I-BAR结构域的基因，我们假设它可能参与膜弯曲和树突棘的形成。在体内，shRNA介导的Mts 1 L敲低阻止了运动诱导的棘和兴奋性突触后电流的增加。我们的研究结果将运动的短期影响与Mts 1 L的活动依赖性表达联系起来，我们提出Mts 1 L是突触活动依赖性重排的一种新效应物。
Exercise is a potent enhancer of learning and memory, yet we know little of the underlying mechanisms that likely include alterations in synaptic efficacy in the hippocampus. To address this issue, we exposed mice to a single episode of voluntary exercise, and permanently marked activated mature hippocampal dentate granule cells using conditional Fos-TRAP mice. Exercise-activated neurons (Fos-TRAPed) showed an input-selective increase in dendritic spines and excitatory postsynaptic currents at 3 days post-exercise, indicative of exercise-induced structural plasticity. Laser-capture microdissection and RNASeq of activated neurons revealed that the most highly induced transcript was Mtss1L, a little-studied I-BAR domain-containing gene, which we hypothesized could be involved in membrane curvature and dendritic spine formation. shRNA-mediated Mtss1L knockdown in vivo prevented the exercise-induced increases in spines and excitatory postsynaptic currents. Our results link short-term effects of exercise to activity-dependent expression of Mtss1L, which we propose as a novel effector of activity-dependent rearrangement of synapses.